Anti-Mullerian Hormone (AMH), a member of the Transforming Growth Factor (TGF)-beta family, has important roles in normal male and female reproductive development. In addition, AMH has clinical applications in reproductive endocrinology and potentially oncology, which has focused attention on the AMH signal transduction pathway, with the goal of identifying new approaches for therapeutic intervention and diagnostics. Like other members of the TGF-beta family, AMH signals by assembling a transmembrane serine/threonine kinase receptor complex of type I and type II components, resulting in the phosphorylation and activation of type I receptor kinase by the constitutively active kinase domain of the type II receptor. The activated type I receptor then phosphorylates the cytoplasmic Smad proteins 1, 5, or 8, which migrate into the nucleus and, in concert with other transcription factors, regulate responsive genes. AMHRII, the type II receptor, and AMH, are mutually specific, while ALKs 2, 3 and 6 serve as type I receptors for both AMH and members of the Bone Morphogenetic Protein (BMP) family. AMH is translated as a homodimeric precursor, containing an N-terminal pro-region and a smaller C-terminal mature domain. The precursor undergoes an obligatory cleavage at monobasic sites between the two domains, but the pro-region and C-terminal homodimers remain associated in a noncovalent complex. Unlike other TGF-β ligands, the noncovalent complex can bind to AMHRII, which induces dissociation of the pro-region.
In the male vertebrate embryo, AMH is responsible for the regression of Mullerian ducts, the anlagen of the uterus, Fallopian tubes, and upper part of the vagina. In the adult male, AMH plays a role in Leydig cell differentiation and function. In females, the role of AMH has been predominantly elucidated in rodents, where it has been shown to have an inhibitory effect on primordial follicle recruitment as well as on the responsiveness of growing follicles to Follicle-Stimulating Hormone (FSH). In addition to its role in normal reproductive physiology, AMH is now recognized as an important clinical marker for diagnosing and assessing reproductive disorders. In females, the serum AMH level is indeed a reliable marker for the size of the ovarian follicle pool and a predictor of the ovarian response to controlled ovarian hyperstimulation.